The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus: Results From the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) Study

Study Questions:

Is excessive weight gain associated with therapy for type 1 diabetes mellitus (DM) prospectively associated with atherosclerotic disease?

Methods:

Data for this study were obtained from the DCCT (Diabetes Control and Complications Trial) and the subsequent observational trial, EDIC (Epidemiology of Diabetes Interventions and Complications). During 1983 to 1989, 1,441 subjects were randomly assigned to intensive therapy versus conventional DM therapy in the DCCT and were treated until the final closeout visit in 1993, a mean of 6.5 years. Annual follow-up in EDIC was initiated in 1994 (EDIC year 1). Participants included in this analysis were a subset of the original 1,441 DCCT subjects who were ages ≥18 years at baseline (n = 1,168), and who elected to continue in the EDIC study. Subjects with type 1 DM (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional DM treatment during the DCCT underwent intima-media thickness (n = 1,015) and coronary artery calcium score (n = 925) measurements during follow-up in the EDIC Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT.

Results:

Excess gainers (fourth quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference. Excess gainers needed more insulin, had greater intima-media thickness (+5%, p < 0.001 EDIC year 1, p = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio [OR], 1.55; confidence interval [CI], 0.97-2.49; p = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (p = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (OR, 1.6; CI, 1.1-2.4; p = 0.01) during follow-up. Increasing frequency of a family history of DM, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment.

Conclusions:

The investigators concluded that excess weight gain observed among some participants in DCCT was associated with sustained increases in central obesity, insulin resistance, dyslipidemia, and blood pressure, as well as more extensive atherosclerosis observed during the follow-up study (EDIC).

Perspective:

These data suggest that in treating patients with DM, monitoring other risk factors including hypertension and lipids should include a regular assessment of weight, in particular increases in waist circumference.

Keywords: Obesity, Abdominal, Atherosclerosis, Hyperlipidemias, Carotid Intima-Media Thickness, Body Weight, Blood Pressure, Weight Gain, Insulin Resistance, Glycated Hemoglobin A, Metabolic Syndrome, Waist Circumference, Dyslipidemias, Diabetes Complications, Body Mass Index, Epidemiologic Studies, Diabetes Mellitus, Type 1, Hypertension


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